Rapid advances in biotechnology have presented unprecedented amounts of new information about the sequences of nucleic acids and proteins. This abundance of information has created an experimental bottleneck. To realize the full potential of the new information, the newly discovered molecules must be characterized in terms of their function, structure, energetics and their interactions. Many of the important determinants of biological function, as well as applications in screening and design of diagnostic and therapeutic agents, are thermodynamic. High-throughput analytical instrumentation is necessary to characterize thermodynamically the vast array of new molecules. Current methods lack the speed and the ability to couple with other devices necessary for high throughput applications. The long-term goal of this research is to address the need for rapid, accurate thermodynamic characterization of biological macromolecules by developing a family of analytical instruments based a new idea called Temperature Profile Spectroscopy. By measurement of optical properties simultaneously over a range of temperature, a reduction of greater than 100 fold in the time required for a thermodynamic characterization of biological macromolecules in solution will be achieved. Development of the Temperature Profile Spectroscopy methodology will permit a significant acceleration in the thermodynamic characterization of biological macromolecules and their interactions, as well as, in the rational design of probe molecules for use in screening and other applications. PROPOSED COMMERCIAL APPLICATION: The research proposed addresses the need for rapid, accurate thermodynamic characterization of biological macromolecules. The method will generate thermal melting profiles of biomacromolecules up to 100 times faster than current technology. This speed is critical for exploiting thermodynamic information in the context of modern screening methods. New experimental protocols also will be supported. The design of the instrument ensures a much lower cost than current instruments.